Telomere shortening and apoptosis in telomerase-inhibited human tumor cells
AUTOR(ES)
Zhang, Xiaoling
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
Despite a strong correlation between telomerase activity and malignancy, the outcome of telomerase inhibition in human tumor cells has not been examined. Here, we have addressed the role of telomerase activity in the proliferation of human tumor and immortal cells by inhibiting TERT function. Inducible dominant-negative mutants of hTERT dramatically reduced the level of endogenous telomerase activity in tumor cell lines. Clones with short telomeres continued to divide, then exhibited an increase in abnormal mitoses followed by massive apoptosis leading to the loss of the entire population. This cell death was telomere-length dependent, as cells with long telomeres were viable but exhibited telomere shortening at a rate similar to that of mortal cells. It appears that telomerase inhibition in cells with short telomeres lead to chromosomal damage, which in turn trigger apoptotic cell death. These results provide the first direct evidence that telomerase is required for the maintenance of human tumor and immortal cell viability, and suggest that tumors with short telomeres may be effectively and rapidly killed following telomerase inhibition.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=317024Documentos Relacionados
- Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death
- Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
- Telomere elongation in immortal human cells without detectable telomerase activity.
- The Yeast TEL1 Gene Partially Substitutes for Human ATM in Suppressing Hyperrecombination, Radiation-Induced Apoptosis and Telomere Shortening in A-T Cells
- Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells